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Biomedical subjects

T Chard

Publications and source records attributed to T Chard.

At least 163 records · Page 9Linked to original sources
PubMed1991

Lack of placental protein 14 production in pregnancy after frozen embryo transfer, down-regulation of anterior pituitary and administration of exogenous oestradiol and progesterone.

The circulating levels of placental protein 14 (PP14) and progesterone were measured in three pregnancies resulting from the transfer of cryopreserved embryos. Two of these women had suppressed ovarian activity as a result of pituitary down-regulation with the luteinizing hormone-releasing hormone agonist (buserelin) prior to treatment with exogenous oestradiol and progesterone. After 14 days of oral oestradiol treatment and if the endometrial thickness was greater than 7 mm, progesterone was given intramuscularly for a further 14 days with embryo transfer on the third day of this treatment. On confirmation of pregnancy by human chorionic gonadotrophin analysis, progesterone administration was altered to transvaginal pessaries for maintenance of adequate progesterone levels and endometrial support. In the two women with ovarian suppression, PP14 levels remained below the 2.5th centile of the normal range for pregnancy. In the third pregnancy, embryo transfer was performed 3 days after a spontaneous luteinizing hormone surge in a normal menstrual cycle. In this pregnancy, PP14 levels were within the normal range. Ultrasonic examination confirmed three normal ongoing singleton pregnancies. These results suggest that the majority of PP14 production in normal pregnancy is under ovarian or anterior pituitary control and that the influence of progesterone is of a secondary nature.

Buserelin↗
PubMed1991

The presence of cation-dependent proteases for insulin-like growth factor binding proteins does not alter the size distribution of insulin-like growth factors in pregnancy.

OBJECTIVE: The aim was to investigate the sera of pregnant women for the presence of specific proteases for insulin-like growth factor binding proteins (IGFBPs) and to determine the effect of these on the distribution of IGFs in the circulation. DESIGN: The method used was the chromatographic and electrophoretic analysis of patients' serum. PATIENTS: Sera were examined from normal women during pregnancy: first trimester (n = 4), second trimester (n = 4) and third trimester (n = 10). Eight women with Type I diabetes in the third trimester were also studied along with sera from ten normal adult volunteers. MEASUREMENTS: Circulating IGF-I and IGF-II levels were measured by RIA and their distribution examined by gel filtration. The pattern and stability of the IGFBPs was investigated by Western ligand blotting. RESULTS: A marked reduction in the serum levels of IGFBP-2, IGFBP-3 and IGFBP-4 on Western ligand blotting, which was associated with the presence of three independent, cation-dependent proteases that were specific for different IGFBPs, was found in late pregnancy. Gel filtration of third trimester serum revealed most of the IGF-I to be present in a complex larger than 130 kDa, with a similar distribution to that found in serum of non-pregnant women. The enzymatic modification of the binding proteins made apparent by the decrease in binding protein bands on Western ligand blotting of preincubated samples had no effect on the distribution of IGF-I following size fractionation. CONCLUSIONS: There appear to be at least three independent enzymes that are induced or activated during pregnancy to modify IGFBP-2, IGFBP-3 and IGFBP-4 sufficiently to prevent their detection by ligand blotting. However, this enzymatic processing does not alter the distribution of IGFs, suggesting that the altered binding proteins are still able to carry IGFs but with reduced affinity. Such an alteration in the carrying mechanism of IGFs may have profound effects upon the bioavailability of the IGFs to the maternal tissues and contribute to the altered metabolic demands of pregnancy.

Blotting, Western↗
PubMed1991

Inter-relations between growth hormone, insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1) and sex hormone-binding globulin in acromegaly.

Acromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF-I, an important mediator of its actions. IGF-I itself is intimately related to insulin both in structure and function. IGF-I circulates associated with specific binding proteins which appear to have important effects on its activity. We have examined the inter-relations between GH, prolactin, insulin, IGF-I and one of the binding proteins, IGFBP-1, in 62 patients with acromegaly of varying activity. Serum IGF-I levels were closely related to the logarithm of mean GH levels (r = 0.76; n = 62; P less than 0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, insulin accounted for some of the additional variation of IGF-I. IGF-I concentrations were independent of prolactin. Fasting insulin levels were high and unrelated to mean GH levels but correlated with those of IGF-I (r = 0.542; n = 57; P less than 0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP-1 (r = 0.684; n = 57; P less than 0.001). Even in subjects whose acromegaly was well controlled or cured, as indicated by GH levels of less than 1 mU/l or IGF-I levels of less than 2 U/ml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality is not clear. Fasting IGFBP-1 levels were low and unrelated to mean GH but were inversely related to fasting insulin levels (r = -0.593; n = 57; P less than 0.001). We propose that a cascade of events occurs in acromegaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1991

The role of vaginal scan in measurement of endometrial thickness in postmenopausal women.

Transvaginal ultrasound scanning was performed on 111 postmenopausal women. Of these women, 103 had postmenopausal bleeding, and eight were undergoing hysterectomy. Of the 103 women with bleeding, 93 had dilatation and curettage (D&C) and 10 patients were treated conservatively with a repeat scan in six months. A correlation of ultrasound findings and endometrial histopathology was possible in 94 patients. In 59 of these (63%) the endometrium was atrophic and the ultrasound endometrial thickness was 5 mm or less. In 29 (31%) patients the endometrial histology was abnormal and ultrasound endometrial thickness was greater than 5 mm. In six patients the endometrium was atrophic, but the ultrasonic endometrial thickness was apparently greater than 5 mm due to intracavity fluid. We suggest that an endometrial thickness of 5 mm is an appropriate cut-off level for conservative management of patients with postmenopausal bleeding, or in screening for endometrial carcinoma.

Aged↗
PubMed1991

Early amniocentesis: alphafetoprotein levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum between 8 and 13 weeks.

OBJECTIVE: The aim was to establish a normal range of alphafetoprotein (AFP) concentrations in amniotic fluid from 8 to 12 weeks gestation, and to determine any difference between AFP levels in amniotic fluid and extraembryonic coelomic fluid. DESIGN AND SUBJECTS: 150 women had a transvaginal ultrasound guided amniocentesis before termination of an apparently normal first trimester pregnancy. Separately identified samples of amniotic fluid and extraembryonic coelomic fluid were obtained and assayed by radioimmunoassay for AFP. RESULTS: In amniotic fluid, very high levels of AFP were present at 8 weeks, levels falling rapidly up to 10 weeks after which there was a slight rise. Thus over the period 8 to 10 weeks, there was a significant inverse correlation between amniotic fluid AFP and gestational age (r = 0.67; P less than 0.001). In extraembryonic coelomic fluid, by contrast there was no trend in AFP relative to gestational age. CONCLUSIONS: The rapidly changing levels of AFP from 8 to 10 weeks as well as the small volume of the amniotic cavity makes the use of amniocentesis impracticable before 11 weeks gestation. The lack of any relation between AFP levels in amniotic fluid and extraembryonic coelomic fluid emphasises the importance of identifying the site of amniocentesis in the first trimester.

Amniotic Fluid↗
PubMed1991

Steroid hormone abnormalities in women with severe idiopathic constipation.

Patients with severe idiopathic constipation are almost exclusively women of reproductive age. To investigate the possibility of a sex hormone abnormality in this condition, we have compared a range of sex hormones during the follicular and luteal phases of the menstrual cycle in 23 healthy women (mean age 33 years) with those in 26 patients with severe idiopathic constipation (mean age 32 years, spontaneous bowel frequency less than one per week). In the patients there was a reduction in the follicular phase of progesterone (4.5 v 4 nmol/l, p = 0.006, median value, controls v patients), 17 hydroxyprogesterone (9.7 v 5.8 nmol/l, p = 0.01), cortisol (387 v 245 nmol/l, p = 0.008), testosterone (2.3 v 1.8 nmol/l, p less than 0.001), androstenedione (10.3 v 8.4 nmol/l, p = 0.02), and dehydroepiandrosterone sulphate (5.1 v 3.0 mumol/l, p = 0.03). In the luteal phase there was a reduction of oestradiol (483 v 350 pmol/l, p = 0.015), cortisol (322 v 242 nmol/l, p = 0.047), and testosterone (2.4 v 1.7 nmol/l, p = 0.003). The concentrations of sex hormone binding globulin, prolactin, luteinising hormone, and follicle stimulating hormone were not significantly different in either phase of the cycle. Women with severe idiopathic constipation have a consistent reduction in steroid hormones.

17-alpha-Hydroxyprogesterone↗
PubMed1991

Purification and assay of insulin-like growth factor-binding protein-1: measurement of circulating levels throughout pregnancy.

Insulin-like growth factor-binding protein-1 (IGFBP-1) has been purified from amniotic fluid by anion exchange, hydrophobic interaction and gel filtration chromatography. The overall recovery of the purification process was 12.2%. The purified IGFBP-1 yielded a single band on SDS-PAGE gel but showed two bands (34 kDa and 68 kDa) on Western blot under non-reducing conditions. Polyclonal antisera were raised by immunization of sheep using the purified IGFBP-1. The best antiserum bound 50% of 125I-labelled IGFBP-1 at a final dilution of 1:500,000. A radioimmunoassay for IGFBP-1 was developed. This assay had a minimum detection limit of 5 micrograms/l, and was used to determine serum levels in non-pregnant and pregnant women. There was no cross-reaction with a wide variety of materials tested. Serum IGFBP-1 levels in non-pregnant individuals (33 +/- 16 (S.D.) micrograms/l) were found to be significantly lower than those in the second (96 +/- 64 micrograms/l) and third trimesters (95 +/- 60 micrograms/l) of pregnant women. During pregnancy, circulating IGFBP-1 levels increased rapidly in the first trimester and reached a peak at 12-13 weeks of gestation (107 +/- 75 micrograms/l). The level then remained at 80 +/- 53 to 103 +/- 70 micrograms/l until term.

Adolescent↗
PubMed1991

The concentration of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in human umbilical cord serum at delivery: relation to fetal weight.

Serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-1 (IGFBP-1) have been determined by radioimmunoassay in the maternal circulation (n = 91) and in the umbilical artery (n = 56) and vein (n = 90) of man. In both the umbilical artery and vein, the concentration of serum IGF-I showed an inverse correlation with birthweight (P less than 0.005 and P less than 0.001 respectively); the mean serum IGF-I levels in the small-for-gestational-age (SGA) group were significantly higher than those in average-for-gestational-age (AGA) neonates (P less than 0.01 and P less than 0.001 respectively). However, maternal serum IGF-I showed no association with birthweight and there was no significant difference between the SGA and AGA groups. These observations imply that the production of IGF-I in the maternal and fetal compartments is independent and that there is unlikely to be transfer of IGF-I across the placenta. Serum IGFBP-1 levels in both maternal and umbilical cord blood (artery and vein) showed an inverse relation to birthweight (P less than 0.001, P less than 0.005 and P less than 0.001 respectively). Increased IGFBP-1 levels in the umbilical artery and vein were observed in the SGA group. These findings suggest that IGFBP-1 might inhibit the action of IGF-I in both the maternal and the fetal compartments and that the rise in IGFBP-1 could be a primary factor in retardation of fetal growth. Alternatively, circulating IGF-I and IGFBP-1 levels may only be a secondary reflection of local tissue events involved in fetal growth.

Birth Weight↗
PubMed1991

The purification and development of a radioimmunoassay for beta-core fragment of human chorionic gonadotrophin in urine: application as a marker of gynaecological cancer in premenopausal and postmenopausal women.

The beta-core fragment of human chorionic gonadotrophin (hCG) is a major part of the immunoreactive hCG-like material found in the urine of normal pregnant women. Patients with non-trophoblastic gynaecological malignancies have been found to have raised levels of urinary beta-core. We describe the purification of beta-core, the preparation of a polyclonal sheep antiserum and the development of radioimmunoassay. The minimum detection limit of this assay was 0.025 micrograms beta-core/l. There was no significant cross-reaction with the free alpha-subunit, hLH, hFSH and hTSH (less than 0.7%), and only partial cross-reaction with intact hCG and free beta-subunit of hCG (6.9 and 18%). Within-assay variability ranged from 2.03 to 12.5% and between-assay variability from 2.25 to 13.4%. The assay was applied to urine samples from 92 normal non-pregnant premenopausal women, 54 normal postmenopausal women and 65 women with active gynaecological disease (47 postmenopausal and 18 premenopausal). In normal premenopausal women the values ranged from less than 0.025 to 0.62 micrograms beta-core/l (median 0.043 micrograms beta-core/l). The values for normal postmenopausal women ranged from less than 0.025 to 0.64 micrograms beta-core/l (median 0.26 micrograms beta-core/l). Postmenopausal women with gynaecological malignancy had values which ranged from less than 0.025 to 4.0 micrograms/beta-core/l (median 0.31 micrograms beta-core/l); premenopausal women in this group had values which ranged from less than 0.025 to 1.15 micrograms beta-core/l (median 0.12 micrograms beta-core/l). On molecular sieve chromatography, the material found in the urine of normal postmenopausal women showed the physicochemical characteristics of authentic beta-core.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Management of a research group.

It is generally believed that research and commerce are unique and different activities. However, the criteria of good business management can also be applied to research programmes, with much benefit to the latter. The objectives of both are fundamentally similar: in one case to produce goods and services, in the other to produce scientific papers. The most successful goods and services, and scientific projects, are those which are closely geared to the desires of consumers--whether the latter be the general public or large organisations. Science, like business, requires good leadership and good people-management. The characteristics of a successful science leader are often remarkably similar to those of a business leader. Individuals within any team must be carefully selected, adequately briefed, and then allowed to proceed with the job in hand. Obtaining resources for scientific research is also very similar to the funding of business activities--all come down to competition between different products and services. The end product of scientific research--the published paper--requires marketing in exactly the same way as a business product. Without such marketing the programme is almost always a failure. The effectiveness of a research programme must be monitored with the same care as would be devoted to a business. If research performance does not reach reasonably defined criteria, then resources are generally withdrawn--the equivalent of a bankruptcy in commerce.

Commerce↗
PubMed1990

Circulating levels of placental protein 12 in ectopic pregnancy.

Maternal serum placental protein 12 (PP12) was measured at the time of presentation in 33 women with a histologically confirmed diagnosis of ectopic pregnancy [tubal pregnancy (n = 29), tubal pregnancy with a live fetus (n = 2), cornual pregnancy (n = 1) and ovarian pregnancy (n = 1)]. All but four of the 33 patients had PP12 measurements within the reference range. Two women had circulating PP12 levels above the 90th centile of the normal range, at 7 and 8 weeks gestation, respectively. One of these had a live ectopic gestation and the other patient conceived after in vitro fertilization. Two remaining patients (one each with a cornual and tubal pregnancy) at 11 and 12 weeks, respectively had levels below the 10th centile of the normal range. It is concluded that regardless of the implantation site, ectopic pregnancy is not associated with depressed maternal PP12 levels, suggesting that the decidual synthesis of this protein is independent of the intimate relationship between decidua and trophoblast.

Decidua↗
PubMed1990

A computer model of antenatal care: relationship between the distribution of obstetric risk factors in simulated cases and in a real population.

The main purpose of antenatal care is to identify risk factors for the fetus. A number of systems have been described in which positive factors are summed to produce an overall risk score for the individual woman. In the present study a computer simulation of a population of pregnant women has been used to examine the use of Bayes theorem to calculate obstetric risk scores. The findings of the computer simulation have been compared with those in a real obstetric population (774 primigravidae; 930 multigravidae). A number of observations have been made which may be of considerable practical significance: (1) in the population as a whole the distribution of risk scores is skewed; most women have a low score while relatively few subjects have high scores; (2) a minimum number of risk factors must be present simultaneously for the risk in an individual to consistently exceed the overall population risk; this number is 4 in primigravidae and 5 in multigravidae; (3) the relationship between the number of risk factors and overall risk does not follow a straight line. The computer simulation provides a test bed in which various assumptions can be examined, such as the effect of removing or redefining given risk factors.

Bayes Theorem↗